The goal of the proposed research is to use an integrative approach to examine the signaling changes, specifically the interrelationships between NO and ROS, that mediate and may influence neurotransmitter activity in renal wrap hypertension. To achieve this goal, three specific hypotheses will be addressed: Hypothesis #1: NAD(P)H oxidase is present and the activity of the enzyme is increased by Ang II and glutamate in the PVN, thus resulting in a" increase of superoxide (O2-) in renal wrap hypertension; Hypothesis #2: Superoxide dismutase (SOD) is present and its activity is decreased contributing to the increase in O2- and a reduction in hydrogen peroxide (H2O2) in the PVN in renal wrap hypertension; and Hypothesis #3: In renal wrap hypertension, there is elevated O2- which combines with NO, reducing NO and ultimately decreasing the inhibitory neurotransmitter GABA; the reduced GABA in the PVN contributes to the rise in arterial pressure. Identifying the changes in these signaling pathways and how they interact to elicit changes in blood pressure would be significantly important for understanding the impact that these pathways have on neurotransmitter activity and hypertension. [unreadable] [unreadable]